Enterotoxigenic Escherichia coli (ETEC) infections are a common cause of severe diarrheal illness in low- and middle-income countries. The live-attenuated ACE527 ETEC vaccine, adjuvanted with double mutant heat-labile toxin (dmLT), affords clear but partial protection against ETEC challenge in human volunteers. Comparatively, initial wild-type ETEC challenge completely protects against severe diarrhea on homologous re-challenge. To investigate determinants of protection, vaccine antigen content was compared to wild-type ETEC, and proteome microarrays were used to assess immune responses following vaccination and ETEC challenge. Although molecular interrogation of the vaccine confirmed expression of targeted canonical antigens, relative to wild-type ETEC, vaccine strains were deficient in production of flagellar antigens, immotile, and lacked production of the EtpA adhesin. Similarly, vaccination ± dmLT elicited responses to targeted canonical antigens, but relative to wild-type challenge, vaccine responses to some potentially protective non-canonical antigens including EtpA and the YghJ metalloprotease were diminished or absent. These studies highlight important differences in vaccine and wild-type ETEC antigen content and call attention to distinct immunologic signatures that could inform investigation of correlates of protection, and guide vaccine antigen selection for these pathogens of global importance.

产肠毒素大肠杆菌(ETEC) 感染是低收入和中等收入国家严重腹泻病的常见原因。 ACE527 ETEC 减毒活疫苗辅以双突变热不稳定毒素 (dmLT)，可为人类志愿者提供明显但部分的 ETEC 攻击保护。相比之下，最初的野生型 ETEC 攻击完全可以防止同源再次攻击时的严重腹泻。为了研究保护的决定因素，将疫苗抗原含量与野生型 ETEC 进行比较，并使用蛋白质组微阵列评估疫苗接种和 ETEC 攻击后的免疫反应。尽管疫苗的分子检测证实了目标典型抗原的表达，但相对于野生型 ETEC，疫苗株缺乏鞭毛抗原的产生、不动，并且缺乏 EtpA 粘附素的产生。同样，疫苗接种 ± dmLT 引发了对目标典型抗原的反应，但相对于野生型攻击，疫苗对一些潜在保护性非典型抗原（包括 EtpA 和 YghJ 金属蛋白酶）的反应减弱或消失。这些研究强调了疫苗和野生型 ETEC 抗原含量的重要差异，并引起人们对不同免疫学特征的关注，这些特征可以为保护相关性的研究提供信息，并指导针对这些具有全球重要性的病原体的疫苗抗原选择。